It is estimated that more than 1.5 million myocardial infarctions occur annually in the United States, and at least 500,000 infarctions result in death, usually sudden. (American Heart Association, Heart and Stroke Facts. Dallas, Tex.: American Heart Association National Center; 1992). Accordingly, myocardial infarction is the most frequent cause of mortality in the United States; and in most Western countries (Coopers, E S. Prevention: The Key to Progress. Circulation. 1993; 24: 629-632; WHO-MONICA Project. Myocardial Infarction and Coronary Deaths in the World Health Organization Monica Project. Registration Procedures, Event Rates and Care Fatality Rates in 38 Populations From 21 Countries in Four Continents. Circulation. 1994; 90:583-612). However, even the optimal use of thrombolytic therapy for myocardial infarction, the advance of which the greatest attention has been focused, could prevent only 25,000 deaths or 5% of the total, because most deaths occur suddenly, before any type of treatment can be initiated. (Muller, J E, et al., Acute Risk Factors and Vulnerable Plaques: The Lexicon of a New Frontier. J. Am. Coll. Cardiol. 1994; 23:809-813).
In 1992, Fuster et al., (Fuster V. et al., The Pathogenesis of Coronary Artery Disease and the Acute Coronary Syndromes. N. Engl. J. Med. 1992; 326:242-250.) classified the progression of coronary atherosclerotic disease into five phases. Phase I is represented by a small plaque that is present in most people under the age of 30 years regardless of their country of origin and that usually progresses slowly (types I to III lesions). Phase 2 is represented by a plaque, not necessarily very stenotic, with a high lipid content that is very prone to rupture (types IV and Va lesions). The plaque of phase 23 may rupture with predisposition to change its geometry and to formation of mural thrombus, these processes by definition represent phase 3 (type I lesion), with a subsequent increase in stenosis, possibly resulting in angina, or ischemic sudden death. The mural and occlusive thrombi from plaques of phases 3 and 4, by being organized by connective tissue, may contribute to the progression of the atherosclerotic process represented by severely stenotic or occlusive plaques of phase 5 (types Vb and Vc lesions). The severely stenotic plaques of phase 5, by a phenomenon of stasis and/or deendothelialization, can become complicated by a thrombus and/or rapid myoproliferative response, also leading to an occlusive plaque of phase 5. Of interest, about two thirds of coronary occlusions are the result of this late stenotic type of plaque and are unrelated to plaque disruption. Unlike the rupture of less-stenotic lipid-rich plaques, leading to occlusion and subsequent infarction or other acute coronary syndromes, this process of occlusion from late stenotic plaques tends to be silent because the preceding severe stenosis and ischemia enhance protective collateral circulation. (Fuster, V et al., The Pathogenesis of Coronary Artery Disease and the Acute Coronary Syndromes. N. En 1. J. Med. 1992; 326:242-250; Chesebro, J H et al., Antithrombotic Therapy and Progression of Coronary Artery Disease. Circulation. 1992; 86 (suppl III)).
Sensitive and specific agents are needed to identify the early stages of plaque formation in a subject, the progression of which can then be delayed or reduced by initiation of an appropriate therapeutic regimen or change in lifestyle.